title: Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study.
abstract: OBJECTIVE
  The combination of carmustine (BCNU), dacarbazine (DTIC), cisplatin (DDP), and tamoxifen (Tam) has been reported in small series to provide a response rate of 50%, but with significant myelosuppression and risk of thromboembolic complications. We performed this phase II study to assess the antitumor activity and important toxicities of this combination in the cooperative group setting.
  
  
  METHODS
  Seventy-nine eligible patients were treated with BCNU 150 mg/m2/d, every 6 weeks, DTIC 220 mg/m2/d on days 1 to 3 every 3 weeks, DDP 25 mg/m2/d on days 1 to 3 every 3 weeks, and Tam 20 mg orally daily throughout treatment. Treatment cycles were repeated every 6 weeks in responding or stable patients for a maximum duration of 1 year.
  
  
  RESULTS
  Twelve objective responses were achieved (response rate 15%, 95% confidence interval 8%-25%). Five responses were complete (CR) and seven were partial (PR). The median response duration was 8+ (range, 4-19+) months, (16+ [4-19+] for CR and 8+ [4-11] for PR), and the median survival of the entire group was 9 months. The toxicities were predominantly neutropenia and thrombocytopenia. Four patients developed thromboembolic events. Two patients died while on protocol therapy, one with complications of neutropenia, and the other with disease progression.
  
  
  CONCLUSIONS
  The activity of this regimen is in the range reported for single agents or DTIC plus DDP, and the addition of BCNU and Tam appears to increase toxicity. We do not recommend this combination for routine treatment of advanced melanoma or as the control arm in randomized studies of combination therapy.
authors.affiliation: City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Margolin
authors.forename: P Y
authors.initials: PY
authors.lastname: Liu
authors.forename: L E
authors.initials: LE
authors.lastname: Flaherty
authors.forename: J A
authors.initials: JA
authors.lastname: Sosman
authors.forename: M J
authors.initials: MJ
authors.lastname: Walker
authors.forename: J W
authors.initials: JW
authors.lastname: Smith
authors.forename: W S
authors.initials: WS
authors.lastname: Fletcher
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
authors.forename: J M
authors.initials: JM
authors.lastname: Unger
authors.forename: V K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000009:adverse effects / Q000032:analysis
chemical_list: D013629:Tamoxifen; D003606:Dacarbazine; D002945:Cisplatin